The family of poly(ADP-ribose)polymerases (PARP) includes approximately 18 proteins, which all display a certain level of homology in their catalytic domain but differ in their cellular functions (Ame et al., BioEssays., 26(8), 882-893 (2004)). PARP-1 and PARP-2 are unique members of the family, in that their catalytic activities are stimulated by the occurrence of DNA strand breaks.
PARP has been implicated in the signaling of DNA damage through its ability to recognize and rapidly bind to DNA single or double strand breaks (D'Amours, et al., Biochem. J., 342, 249-268 (1999)). It participates in a variety of DNA-related functions including gene amplification, cell division, differentiation, apoptosis, DNA base excision repair as well as effects on telomere length and chromosome stability (d'Adda di Fagagna, et al., Nature Gen., 23(1), 76-80 (1999)).
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid and protein phosphatase. PTEN functions as a protein phosphatase by dephosphorylating protein substrates on serine, threonine, and tyrosine residues (Myers et al., Proc Natl Acad Sci USA 94:9052-9057 (1997)). PTEN functions as a lipid phosphatase by dephosphorylating phophoinosital 3,4,5-triphosphate (PIP3), a key signaling component of the phosphoinositol-3-kinase (PI3-kinase) pathway (Maehama and Dixon, J Biol Chem 273:13375-13378 (1998)).
PTEN is a known tumor suppressor that has been implicated in cellular processes including mediation of the MAP kinase signaling pathway, centromeric maintenance, and is implicated in DNA repair pathways through mediation of Rad51 gene expression. (Gu et al., J Cell Bio 143:1375-1383 (1998); Weng et al., Hum Mol Genet (2001); and Shen et al., Cell 128:157-170 (2007)).